Related Experiment Video
Updated: Jun 14, 2026
Stem Cell-Derived Viral Ag-Specific T Lymphocytes Suppress HBV Replication in Mice
Published on: September 25, 2019
Single-cell multimodal analysis reveals the dynamic immunopathogenesis of HBV-ACLF progression
Xi Liang1, Jinjin Luo1, Qian Zhou1
1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Background:
Acute-on-chronic liver failure (ACLF) is a life-threatening syndrome involving dysfunction of multiple immune cell types.
Objective:
This study aimed to comprehensively depict the dynamic trajectory of immune responses throughout the disease course of HBV-related ACLF (HBV-ACLF).
Design:
Single-cell RNA sequencing and single-cell proteomics were performed on the peripheral blood mononuclear cells of 45 samples from 17 patients who were hospitalised (progressive/stable/recovering course of HBV-ACLF, 6/5/6) and 15 control subjects (liver cirrhosis, chronic hepatitis B and healthy controls, 5/5/5). Functional and mechanistic experiments were validated in vivo and in vitro.
Results:
Single-cell multiomics analysis revealed specific changes in the peripheral immune response in ACLF. VCAN+CD14+-monocytes with activated interferon-stimulated genes and enhanced inflammatory functions, stimulated by HBV relapse and expanded in ACLF-1, fuelling early inflammatory storm. The subsequent apoptotic hepatocytes predominantly induce hyperinflammatory C-X-C motif chemokine receptor 2 (CXCR2)+-neutrophils and CD163+-monocytes, enriching in patients with progressive ACLF and serving as significant markers of disease deterioration. Cytotoxic T-cells were functionally impaired and significantly decreased in progressive patients. CXCR2+-neutrophils exhibited immunosuppressive activity and induced the exhaustion of cytotoxic T-cells. Pharmacological inhibition of CXCR2 significantly reduced neutrophils infiltration, restored cytotoxic T-cells and showed therapeutic effect in ACLF mice. Six immune cellular modules (CMs) were identified for patient stratification, with CM2 and CM6 showing strong predictive value for disease outcomes, and CM3 indicating a potential early therapeutic window.
Conclusion:
Our longitudinal multiomics study revealed the dynamic evolution of the immune response in HBV-ACLF and characterised diverse immune patterns for the future precise management and therapeutic intervention.
More Related Videos
10:37Analysis of HBV-Specific CD4 T-cell Responses and Identification of HLA-DR-Restricted CD4 T-Cell Epitopes Based on a Peptide Matrix
Published on: October 20, 2021
11:34A Competent Hepatocyte Model Examining Hepatitis B Virus Entry through Sodium Taurocholate Cotransporting Polypeptide as a Therapeutic Target
Published on: May 10, 2022
